Explaining the vaccines, and how milk banks work

Kalipso Chalkidou of Imperial College gives us an overview of the frontrunner COVID-19 vaccines, how they work, and what hurdles are left to overcome, and Natalie Shenker of Hearts Milk Bank explains the work done by the charity.

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Transcript

This transcript was automatically generated using speech recognition technology and may differ from the original audio. In citing or otherwise referring to the contents of this podcast, please ensure that you are quoting the recorded audio rather than this transcript.

Jessamy: Hello and welcome to a new episode of The Lancet Voice. I'm Jessamyn Bagonall. 

Gavin: And I'm Gavin Cleaver, you'll have been barely able to move for news and comment about COVID 19 vaccines over the last few weeks, which is why we thought it'd be a good idea to have Professor Calypso Chokadu, Director of Global Health Policy at Imperial College London, lay out a guide to the vaccines for us, what they are, what we know, and what comes next.

Jessamy: Calypso, thanks for joining us again. We have these new sort of four vaccines saying that they've got good effectiveness against the virus. We don't really have the details yet, but it's great news. And we've heard from lots of people why it's such great news. But perhaps in your own words, from your background in global health and drug regulation, you could walk us through the significance of what's happened over the last couple of weeks.

Kalipso: Sure. As you say, there's there's four vaccine candidates which have shown promising results in trials. So these are all results from phase three trials. So these are large trials done on large numbers of individuals, some of whom are given the vaccine. Some are the controls.

They're not given the vaccine and they're followed prospectively. into the future. And then as episodes of illness, severe or less severe perhaps, and we can talk a little bit about that occur, then the results accumulate and the companies who are sponsoring these trials can look at those results and draw conclusions as to the effectiveness of the vaccines, how well the vaccine works in preventing disease from COVID 19.

So this, these are the results that we're getting now. And they're very promising for for those candidates you mentioned. So we've got two mRNA vaccines one from Moderna and the other one for Pfizer and BioNTech. And we can talk a bit more about what an mRNA vaccine is. And then the AstraZeneca and Oxford vaccine, which is an adenovirus vaccine and also the Sputnik, the Russian vaccine sponsored by Russia's sovereign fund, I understand, which is also similarly an So 

Jessamy: maybe you could tell us about these two different platforms, both of them very novel things that we don't really have vaccines for in, in other fields.

What are the sort of pros and cons from your point of view from a kind of access and equity point of view of the different platforms, right? So as you say, 

Kalipso: both platforms are quite quite new, unique, and haven't quite been used previously in humans for this purpose of for any purpose of vaccination or drugs.

Certainly the RNA mRNA platform is very, very new. Now the, they have obviously commonalities in that the, both types of vaccine are meant to prevent disease and perhaps also may affect prevent transmission. And these are two different kinds of outcome which we could discuss a little bit further because it it, it is quite important to differentiate between the two, but in terms of equity, as you say, or access accessibility.

especially to resource constraints settings. They are quite different. The mRNA vaccines require quite low temperatures. So the Pfizer one minus 70 Celsius degrees Celsius. Moderna is also I think minus 20 or so, so very low temperatures to preserve them and move them around. So the so called cold chain requirements are quite extreme certainly for the Pfizer vaccine, making it harder perhaps to see how.

They could be transferred and distributed in, say, across Sub Saharan Africa, South Asia, or even Latin America, at least for the time. Though that said, both companies, Moderna and Pfizer, are saying that they are looking at the so called thermostability, so trying to look at whether there are formulations that are more resistant to normal temperatures, which would then make the product more accessible.

On the other hand, the adenovirus vaccines. Are easier to transport in that they require a normal sort of fridge. and they could also survive in room temperature for quite a while. So you can envisage a situation where things can be moved around much easier in in settings that are quite limited in terms of resources.

So that in terms of accessibility, that's quite a big advantage. There's other aspects. So price, for example, is quite important. We know that lots of high income countries and coalitions of countries of the EU coming together to make this sort of so called advanced purchase commitments with companies or committing to buy a certain volume of the vaccine once it becomes licensed at a certain price.

The price is not transparent, so we don't really know what the prices are for each one of those deals. But what we do know is that AstraZeneca is saying that it will make its vaccine available. On a not for profit basis whilst the outbreak is raging and for low income settings forever. As I said, they're committing to make it available for poorer settings effectively at cost.

Whereas Pfizer which didn't receive much of public investment, at least for early R& D, though it is part of those advanced purchase commitments, is actually pricing higher up, perhaps 10 or 15 times higher than, per dose than the AstraZeneca vaccine. Around 20 or so per dose which, which then raises issues as to again affordability because we're looking here, billions of doses that need to be purchased and distributed in in developing country settings.

So that's a second obstacle perhaps in getting the vaccine to people. 

Jessamy: And I guess just following up on that, we talk a lot about pricing of drugs and whether it's fair or not. Where do you. Where do you sit on this? Obviously, there's been, to get to these novel platforms, there's been huge investment from public funders beforehand, whether it's looking at sort of potential HIV candidate, vaccine candidates, or whatever, there was a great foundation for these platforms to be able to then be taken by pharma companies and made into something.

But the initial foundation has been largely public funded. Where do you stand on Just from a moral point of view on, on pricing with these things, just out of interest. 

Kalipso: Yeah, I think public investment is significant direct public investment or, but also indirectly making the infrastructure available, training people, universities, for instance, scientists, right?

All of that is part of being. part of society and having a strong government that invests in infrastructure and companies benefit from that. At the same time, they also pay tax and they employ lots of people to contribute to the growth of an economy. I think there's quite a lot of effort that's gone on the part of industry, the pharmaceutical companies into those platforms, certainly the mRNA.

So Moderna, for instance, never had a vaccine licensed at all. So for years they've been investing, raising funds. investing in this type of platform, which if proven to be successful, could be used for all sorts of other things as well, not just this particular COVID virus. So I think that it's quite important that the pharmaceuticals markets as.

is well regulated in terms of quality and effectiveness of showing your regulators need to be able to force companies to produce convincing information evidence as to whether the products work and how well they work in which population. So that's quite important but also regulated in terms of price.

How do these prices get set whether they reflect if you like the health benefit that they bring to population? So there's a big conversation going on as to appropriate pricing obviously has been going on for years And it's still continuing in relation to the vaccines. My view is that there needs to be An assessment of the benefits that the vaccine it's type different type of vaccine different kind of vaccine confers health benefits to start with, because obviously societal benefits of if indeed it holds the outbreak are great, but I think there's very little.

Arguments, it's not particularly, it's not clear to me why all of that societal value should be appropriated by industry. However certainly in terms of the health value I think a large chunk of that couldn't, should go to industry. I don't believe that companies, need to be coerced to give away their IP at this point in time so that governments have the vaccine for free.

Or not for free, but as you say, having paid what they've contributed effectively now get it a zero price. I think it's important that the market is sustained, but at the same time, I think that market needs to be controlled, regulated through an assessment of the evidence of how these vaccines work and for whom.

And I don't see much of that happening, which worries me. It doesn't, it's not happening in terms of the advanced market commitments. And it doesn't seem to be happening now, prospectively in terms of how these choices will be made amongst all these candidates and more to come. In terms of their characteristics, trade offs between different attributes and then of course the price.

So I don't see that happening and that worries me. 

Jessamy: Yeah, agreed. So that kind of really rigorous sort of assessment. scientific approach to assessing these different candidates. I suppose it's, people have been waiting for so long that there's just huge excitement and it seems to be fairly chaotic different responses to all of this sort of news that we've got candidates at, not unexpectedly, such good results.

Kalipso: If maybe what shocks me really annoys me incredibly is that despite the significant amount of funding that's gone into all of this by governments And, of course, the great, impact on business more broadly, including the pharmaceutical business of the outbreak, if we were to continue unchecked.

Despite all of that and the global interest in this work, there's still very little standardization and enforcement of reporting of results beyond investors for example. Which is really problematic, so we don't have results effectively reported in a way that allows peer review that allows comparison across alternative candidates.

All we're getting is drip, drip fed being drip fed sort of information by companies through investors for in the name of confidentiality. I can understand the rationale that they're doing this in order to control stock markets and share prices, but ultimately this is a public health emergency.

The share price is important, but what we do need to see is these companies reporting in a standardized way, including the way they're using the assays and the way that's comparable and verifiable, the results in order for regulators and the broader scientific clinical community and the media and the press and the people, all of us.

To understand ultimately what these things are doing and how they compare to one another. And we haven't really seen much of that happen. So before we go to the IP question, I would feel quite upset about the, how limited and how, as you say, chaotically this information is being communicated in a very conflicted fashion.

So far, and a point to make also about the IP is that as you said, if you take the mRNA platforms, for instance, this is a sort of a platform which is not specific to that, to this particular product. So if it works, it could well work for all sorts of different products, including vaccines. And if it becomes thermostable, then it would revolutionize vaccination also for developing nations, certainly Sub Saharan Africa, South Asia.

If they were to hand the IP over, they'll be handing over effectively all the different, the IP for all the different products that could be developed in future. It's quite it's a tricky, it's a very special situation. And then the other point to make about IP is it's not as simple as giving the recipe away.

There's also IP in terms of manufacturing which is held by different partners. And that also comes with significant requirements to invest in in know how and expertise in people and infrastructure, very sophisticated labs, which are not easy to set up from scratch, even if one had the manufacturing IP.

So we're looking here, it's not a simple sort of dichotomous situation where Pfizer hands over the IP and then all of a sudden. People across Africa start to manufacture their vaccine, giving it to people, going way beyond the cold chain requirements, even upstream in terms of manufacturing scale up.

These are difficult things to do very highly specialized that require expertise in terms of people and facilities that don't exist right now. In, in most, in, in any developing nations. 

Jessamy: So I suppose on that point, as you say, we do need to see the data for all of these different vaccines and we're looking forward to seeing that data.

I think the whole scientific community is looking forward to seeing that. But assuming that, the data is not too dissimilar to the sort of drip fed press releases that we've had, what should governments and health ministers be doing right now to prepare for a potential vaccine candidate that might be available, in, in real time, in real life, in, in just a few months time or six months time?

Kalipso: I think it's a hugely complex exercise logistically in terms of getting the vaccine out there, distributing it getting people to get it. And that's yet another element of communication of risks and convincing people that's an important thing. For them to do. And you can talk a little bit about that, but momentarily, perhaps you could look at upstream all this the situation in relation to choosing a vaccine or an unfortunate situation, which is assuming, as you say, this thing all.

get confirmed and there's no safety signals and indeed the effectiveness is confirmed. We'll be in a situation where we can actually choose between different vaccines. The Johnson candidate is close behind. There's two Chinese products, one of which is quite advanced as well. We could have a whole series of portfolio vaccines that each one has different characteristics in terms of efficacy or effectiveness, perhaps in terms of safety by some population.

So some of them may work better in older people, some in younger also differences in terms of, the nature of the effectiveness. So the AstraZeneca vaccine early results again, not unverified, suggest that perhaps it does play a role in stopping preventing transmission from asymptomatic carriers.

Now, that is very important. because really ultimately what you want to do to be able to do is to to stop this thing being transmitted as opposed solely to protect people who are likely to experience it severely and perhaps die from it. There's also going to be differences between candidates in terms of the price, as you said, in terms of the logistics of transporting it, manufacturing it.

So some of these products will be relatively easier to manufacture. Johnson has a deal with Aspen in South Africa to manufacture vaccine, the vaccine locally. And this could be, could mean a regional reach across Southern Africa, whereas, as I said, the Moderna product could potentially be extremely difficult to manufacture in the short term.

The longer term may well happen, but in the short term in Africa. So there'll be differences in terms of manufacturing, differences in terms of distribution, the cold chain requirements, even in terms of administration. In some cases, you'll need. Specialized people who have specialized knowledge to administer the product.

That's on the vaccine side. And then on the on the countryside, you'll be differences in terms of infrastructure, in terms of human resources, in terms of clinics, distribution, ability to reach out or run mass vaccination campaigns. Differences in terms of the characteristics of the population in this country, younger, older, with more comorbidities or fewer comorbidities there's also obviously differences in terms of country's ability to pay whether they are part of COVAX or not, and we can talk about that.

There's still a good discussion of a core financing element. And there'll be differences in terms of seroprevalence, so it could well be that in certain settings, say urban settings you might find in some countries, and I'm seeing this from reports from Southern Asia from Kenya, that a lot of people have been exposed to the virus and may be, may well be immune to it, so there could be a conversation to be had, especially if we don't have enough doses for everybody in the first instance as to how do you target the vaccine, who do you give it to.

There's a lot of parameters are very difficult to make these decisions by, talking through the options like we're trying to do now. So what, in answer to your question, long answer is that countries need to set up mechanisms, national task forces similar to the NITAGs, the National Immunization Advisory groups or similar to NICE c, our joint vaccination immunization committee, which can come together for their countries multidisciplinary, look at the different information, the different products and make a decision as to which vaccine or vaccines they're going to prioritize.

And then downstream of that, there's all the discussion, of course, of how you get into people, et cetera. And I don't see much of this happening. Covax hasn't quite, or Gavi. Haven't really boosted any such capacity. WHO is not doing much in this space either. I think they're trying to look at the different products more global level as opposed to being able to issue.

a country specific guidance, but that's exactly what is needed. Every country needs to make a decision for itself. And it will be very difficult if these decisions are, seem to, are really imposed by somebody outside the country saying you're Rwanda and you need to have this and you're Malawi and you have that.

And that would be very 

Jessamy: problematic. I think that those are some excellent points. Where are we with COVAX? I think COVAX has 

Kalipso: obviously continued to raise resources, which is wonderful. It's great. I don't, I still don't think there's enough money in the pot to cover everybody in the low and middle income countries that are participating.

I think there's questions still as to COVAX's sort of ability to negotiate prices if you take the Pfizer product, it's not in COVAX's portfolio, obviously they're having discussions, but the, the, they're not, I don't think strong enough purchasers, to negotiate a price.

Say, as compared to northern nations. And also, as I said earlier I don't see COVAX setting up or supporting countries set up those processes that would allow an independent and country sensitive approach to assessing alternative products, country by country. And obviously that's difficult to do, but over the years GAVI supported NITAG.

So this is the sort of committee that you need to revive. to allow for this process to take place. And I don't see that happening. Certainly not supported centrally. And that's quite problematic. I think obviously it's the only coalition that supports middle income, low middle income countries.

I think that's, it's wonderful that they're there, but I think at the same time, we're seeing a lot of bilateral deals happening, even amongst middle income nations whether they go directly to China, Russia, or other companies. And I think that's again quite problematic. A lot of the time these deals are happening with multilateral development bank money or World Bank money.

And it really again worries me in terms of the processes, the governance of the whole process. a selection process, the procurement process, the distribution process, who is considering all these factors at country level who's supporting countries make these decisions. It's not clear to me.

Jessamy: I agree. It does sound worrying. Last time We identified some countries that we were concerned might not fit either thing. They might not be able to fund their own vaccines by buying them directly in unilateral deals. They might not be able to get it through COVAX and you've mentioned it there, but you were saying, whether they go to China or whether they go to Russia, maybe you could just talk us through what that process is, say for a country like Brazil or, a.

a middle income country that's looking to try and buy vaccine for its population? 

Kalipso: Yeah, lots of middle incomes certainly Latin America are joining COVAX or have joined COVAX. But to say that, I was talking to colleagues from Colombia a couple of weeks ago when they were saying that obviously the procurement process is critical and being able to have some support.

From COVAX is quite important. At the same time, and access to a diversified portfolio, which Colombia couldn't have done it on its own. But at the same time, Colombia will have to pay. At least in part, probably the whole, a whole amount. So how, again, does Columbia decide which product is appropriate for itself and how does it negotiate a good price?

And then the logistical details, getting this thing out to people. Are massively complex and and a huge issue which COVAX is not obviously going to solve for Colombia. So that's also part of it. But, if you take Indonesia, for instance, where right now they are seeing a big peak with the health system rather overwhelmed, lots of cases they are they've announced a mass vaccination campaign to start before the end of the year.

And they've effectively, they've made a deal with China to get one of the Chinese products. So how would, how did Indonesia go about that? That these are the sort of bilateral deals with or without external support, be it World Bank. World Bank made available 12 billion recently to countries for procurement and rollout of vaccines.

But it didn't make it a requirement that this this money ought to go through COVAX. So in, in essence, it's allowing national procurement processes to run this or indeed bank facilitated procurement. And there's lots of risks related to that. So a country like Indonesia could well borrow money or have some form of a deal with China.

We don't know exactly on what basis. To get enough doses to, to distribute to its population. And it, they would go ahead and do that. Whereas other countries who, that are smaller and obviously, don't have the volumes of Indonesia will have to stick with with COVAX.

And then again, the question is, who decides for these countries? How are they engaged in the process? What is the process of deciding? All of these things are. very vague and non transparent right now. 

Jessamy: So in an ideal world, what would happen in the next six months? In an ideal world, 

Kalipso: I think there would be a lot more assertive regulators, certainly the European regulator, the UK regulator, the Americans, the FDA.

Would really with support from their respective governments demand certain start standards, including standardization of reporting requirements for this data to be put in the public domain of all the different vaccines and independently assessed. We'd have ideally also submissions made to the World Health Organization pre qualification process, the same sort of regulatory process.

And AstraZeneca said of the companies so far, AstraZeneca is the only one I'm aware of that committed to submit a dossier to the World Health Organization because many. Developing countries are looking to WHO for that regulatory signal. So we'd have better standards for reporting and independent review of the data globally.

And at the same time national processes for assessing the costs and benefits of different products given this information and other information the countries collect local locally, domestically. And clear criteria as to who's choosing what and for what purpose, what reason and then the process of negotiating with the government, with the companies to get the product.

Unfortunately, this is a wish list that probably will not materialize. And what we're likely to see and we're seeing is emergency use authorization now being used as effectively. The regulatory approval mark which is very unconventional. You'd expect a lot more information to be made available before a company gets conditional or full approval.

Now, we'll probably be seeing those front runners not the Russian product, but certainly the mRNA ones and potentially AstraZeneca here in the UK getting emergency use authorization. And then on from there, already these companies have started producing significant numbers of doses. And I suspect that the vaccine will be rolled out and large numbers of people vaccinated in the US and the UK and elsewhere, certainly in the northern hemisphere.

So that's what we're likely to be seeing. Whilst in the meantime, COVAX will continue to try and broker deals with the most appropriate products for other countries and some of them, large middle incomes will be making their own deals. With companies, alongside the likes of the UK and other countries.

Jessamy: So what's your biggest concern or what are you most worried about that might happen over the next couple of months? 

Kalipso: I'm worried about, all the the known unknowns, if you like. We know that there's a lot of things we don't know about safety and efficacy. I'm worried that perhaps this will become, it will stay unknowns forever in that if through emergency use authorization companies start.

And blinding and then their products, the first entrance set the bar and their product becomes the norm, the comparator. I think this would make it very hard for second, third generation, second generation products to come in because they have to compare themselves against Pfizer's product. It will also mean that you might not get, ever get good enough information on safety and efficacy, certainly on efficacy in relation to.

reducing transmission because for that we need large numbers of people. We need these big trials to continue for quite a bit to be able to elicit whether the vaccine is working in that way. So I'm worried that regulators will fast track approval and this will affect. Both the marketplace in terms of second entrance, which are important and we need more vaccines to come in, but also in terms of evidence for this first entrance.

So which will in turn, perhaps make it less easy to convince people. that the vaccines are working and they should take them. Ultimately people need to be convinced that they won't take these things to, for them to work. They're not enough. It's not enough that they're produced. So my concern is the, how regulators and governments are behaving right now.

They're not worried enough about uncertainty. at this point in time. 

Jessamy: Yeah, that makes sense. And we've mentioned a couple of times, so just to finish, on this issue of a vaccine stopping or reducing disease severity or stopping transmission, just tell us the two different, those two different things and how we would be able to assess.

Kalipso: So far from the interim results of the Phase 3 trials that we're looking at, the candidates reporting results are really reporting the effect of their product on reducing symptoms. And in the majority of cases it's relatively mild or moderate symptoms of the disease of flu like symptoms of COVID.

In in the case of Pfizer, there's also a small number of cases, 10 cases in total, where they've shown protection against severe symptoms. That's quite important. So we want, it'd be good to have a vaccine which protects people, prevents them from experiencing ideally not just the moderate symptoms, but the severe symptoms, which would then lead to hospitalizations, admissions into intensive care units and potentially death.

We haven't really looked at that as an outcome yet. But that's quite important. Now, in parallel to this, and they're not mutually exclusive, but they're not necessarily, they don't need to, when one happens, the other doesn't necessarily happen is the effect of the vaccine on transmission.

So really you also want a vaccine. which stops people from transmitting. Especially people who are asymptomatic who know that with COVID, a large chunk of the population who's doing the transmission are actually not aware they have the disease. So once you start having symptoms, you ideally, that you need to protect others, you need to self isolate, etc.

But a lot of the transmission happens whilst people, before they start exhibiting symptoms, or indeed people who never exhibit at least serious enough symptoms for them to notice them. And so they transmit unknowingly. Now the AstraZeneca vaccine suggests the results, early results suggest that perhaps those asymptomatic individuals, the viral load effectively those individuals is coming down thanks to the vaccine.

But again, you need large trials where you basically be able to show them the community setting the vaccines actually preventing outbreaks, which again, is very difficult to do. And at the same time, or you need. This sort of data on sort of prevalence to see whether people and viral loads to see whether people actually become from asymptomatic, symptomatic, and also to see whether they're shedding the virus, whether they're transmitting the virus.

Or not. And these are complex outcomes were quite important. In terms of the nature of, the profile of the product and what the impact it might have. So to give you an example, let's say that Pfizer's vaccine or one of the vaccines that comes through first does a great job protecting people from becoming severely ill or ill, but it doesn't reduce transmission.

So you could. This is a situation where actually you have more asymptomatic people because the vaccine does a great job at preventing symptoms from exhibiting whether they're mild or severe. So people may well have the virus transmitted. but not know about it because they're not exhibiting any symptoms.

So this vaccine is protecting them then. It prevents them from being admitted to hospital, and experiencing severe disease, but it doesn't protect others from transmission. So if behavior of people then think, oh okay, I've been vaccinated. We're all vaccinated. It's all fine. If I'm a health worker vaccinated, I could end up actually transmitting the disease to to lots of people et cetera, et cetera.

It'd be an interesting situation if we were to have to say to people look, you're all, and we're all being vaccinated, but you need to continue wearing masks, washing your hands, social distancing, working from home. You might see that this might be difficult then to comprehend given all the hype around the vaccines.

So it's quite important to understand what the vaccines are actually doing. And it's quite important for that. We need to get, keep the trials running. 

Gavin: So just a fantastic interview with Calypso and a really great overview of where we are with all the vaccines. But of course, in the few days since we recorded that interview, things have moved on again.

Jessamy: Yeah, exactly. We now have approval in the UK for the Pfizer vaccine to be rolled out. And in fact, I think in some places on Monday, which is Monday, the 7th, that Healthcare workers will start having it, I think, up in the north of England, I've heard. So a lot has already changed. But actually, it doesn't really take away from the main messages that I think Calypso so articulately framed.

Which is that we're still a long way from rolling this out to everybody. Tedros is we're not all, we're not safe until we're all safe is point is crucial and in terms of equity to access, there's still many countries who are going to be a long way from getting a vaccine.

And also just the one about caution and the fact that, regulators and everybody still needs to bear in mind that there's a lot that we don't know about the vaccine in terms of transmission. And we need to follow this up with, continued robust research. 

Gavin: It's important to emphasize, isn't it, the caution that's still necessary.

We're not relaxing measures anytime soon over the next few months, and while we keep being given this particular target, in Western countries of roughly Easter, for things to start easing up, that's still a few months from now, and life won't be noticeably different for a lot of people until then.

Jessamy: It's extremely difficult line to tread because obviously it's exciting news that we've got these vaccines. It's important. It's a huge step. And it means that, we can see the end in sight. But at the same time, we need to balance this encouraging people to have the vaccine saying, it's safe.

We've got the evidence to say it's safe. It's good. But at the same time, be cautious enough to know that we need to continue the trials. We need to find out about transmission. And we need to keep people doing non pharmaceutical interventions like social distancing and mask wearing in the interim. So it's a very difficult public health message to balance.

And I think it's not one that I've heard many countries. Balancing very well, but that's got the right tone of either being, this is great. It's ending now or, this is terrible. And obviously we need that balance. We need people to have the vaccine. We need that encouragement.

We need that safety signal, which we have now. But we also need to bear in mind all of the other things that will need to continue happening in the interim. 

Gavin: is I feel like in 2020 it's been difficult to get the nuance across a lot of the time and this is a very nuanced message on the one hand you've got obviously a lot of triumphalism at the production of these vaccines so quickly although obviously so much research has gone into the base of these vaccines anyways not like they were particularly they were produced quickly but not as quickly as a lot of people are making out but also the we need to express caution while expressing happiness that the end is in sight and while the end is in sight there's still 

Jessamy: Yes, I think there will be a lot to reflect on from this year in terms of how we communicate nuance and health messages with the public and I hope it will spur on a lot of research and a lot of evidence that we can improve on for the next time we may face this source of situation, whether it's, climate change issues or anything else, we have to have a way of being able to communicate with the public effectively about important, very crucial, but nuanced health messages, which mean, or which require them to change their lifestyles.

And I don't think that we've We haven't figured that out yet in the sort of technology, misinformation, digital age that we live in at the moment.

Gavin: Donor Human Milk Services, or Milk Banks, offer the opportunity of being fed with human milk to every baby who could benefit from it. There are countless interesting stories behind Milk Banks. And our Lancet voice board member Dr. Lanlan Smith has personal experience. Here she speaks with Dr. Natalie Schenker of Heart's Milk Bank about the charity and how it operates.

Lan-Lan: So hello, I'm Dr. Lanlan Smith, the editor in chief of the Lancet Haematology and I am absolutely delighted today to be joined by Dr. Natalie Schenker who is one of the co founders of the Heart's Milk Bank and we are going to be talking today about the topic of milk banks for the Lancet voice. So just to give you a little bit of background about me and why I am interested in milk banks and how I got involved with this.

So my son was born about two and a half years ago and I had a really difficult breastfeeding journey and he had a tongue tie. I had postnatal depression. It was all really difficult and it was with the help. of some, a really great group of international lactation breastfeeding consultants that I was able to salvage our breastfeeding journey and continue long beyond the six months that I had originally envisaged.

And it was fantastic. And through that really supportive network, I've got to know people with the heart's milk. Bank and the Human Milk Foundation. And last year, I helped do some fundraising for them by running a half marathon to, to raise funds for them. And that's how I got to know Natalie. And I am thrilled to be able to talk to you today about to, so you can tell us a little bit about all the great work that you do.

So thank you. It's great to be able to talk about this. Yeah shall we start off with the basics? So just what is a milk bank? Okay 

Natalie: A milk bank is, operates almost exactly like the blood transfusion service. We're safety driven, and what we do is recruit milk donors who have surplus milk to what their own baby needs, and that might be for a variety of reasons.

They are screened, they have serology tests, and then we collect their milk, screen it microbiologically, and then heat treat, pasteurize the milk to basically destroy potential for harmful pathogens. And then the purpose of milk banks over the last few decades since the 1980s has largely been to support very sick, very low birth weight premature babies on neonatal units.

But the history of milk banking is quite interesting. I don't know if that's something you'd like me to go into. Yeah, definitely. 

Lan-Lan: I'd love to learn more. 

Natalie: So something That I learned when I was setting up the Hearts Milk Bank and talking to a lot of community groups. All the 18, 90 year old women would throw their hands up and say, Oh, but this is just what we used to do.

And it turned out that in the UK, milk banking was fairly ubiquitous as a service. in the 1960s and 1970s. It was just how babies who were born in hospital whose mothers didn't have enough milk were fed. And it was relatively informal. In most instances, it was just the case of a mother being asked to give an extra expression of milk for another baby.

Sometimes that milk was heat treated in a pen. And some milk banks had formal pasteurizers and teams who were trained to be able to do that. But then the advent of HIV in the 1980s and the pandemic of that meant that safety became much more of a concern. And knowledge that breast milk was a way that HIV could be transmitted meant that within a few years, any milk bank that didn't have a pasteurizer and a team that was trained effectively shut down.

So in the UK, by 1991, there are only six milk banks left. And then when it came to look at how milk donor milk should be used, it was really rationed for those babies for whom it could be most efficacious. So those very low birth weight babies who are high at high risk of a disease called necrotizing enterocolitis.

And I guess one question I've struggled with is why wasn't there more medical drive to keep milk banks open to support other babies and particularly to support their mothers? And largely that was because certainly my own medical training during the 1990s emphasized that really Preterm formula was just as useful that it was a way that electrolyte balances could be monitored, fluid levels could be monitored.

It's a lot more practical often than breastfeeding. And so although we knew we were taught that breastfeeding had benefits, they really weren't placed as highly as perhaps they should have been. Certainly in my training and certainly in the training that we have now. So milk banking can be expensive and.

Preterm formula is obviously very cheap, infant formula is very cheap in comparison. And so that largely led to milk banks staying as small as the services they were. 

Lan-Lan: Yeah, I was interested when you were talking about that, I was interested. It was like how much of that has to do with the rise of milk substitutes and that industry taking off?

Natalie: Absolutely. They took a big hit during the 1970s in public opinion, but also in sales. And so when the companies were looking for how to come out of this economic hole, then diversifying their portfolio was the obvious choice. And by creating specialized formulas, which are actually from a biochemical perspective, not that different at all to full term formulas, they could market those and target the medical community to use them.

Lan-Lan: Yeah, that's something I certainly did not know before I had my first child. I saw all these ads for different formulas, follow on formulas. And I thought, Oh that's interesting. But then once I actually learned a little bit more about the topic, it's no, if you do. need to use these milk substitutes.

The newborn stuff is all that you need. But anyway, we're getting off topic a little bit. My own 

Natalie: ignorance as well. I had no idea about any of this until I had my first baby. And that's having worked in neonatal units and Peds units in several hospitals and worked in Peds surgery myself. Almost nobody knows this and it's something that certainly medics should be much more aware of.

Lan-Lan: Yeah, so can you give us a little quick rundown of the main advantages for using a donor milk over milk substitutes? 

Natalie: Sure, so it's a really exciting time to be in the field, mainly because of the growing understanding of how early life exposures helped pattern the life course over a lifetime, the concept of developmental origins of health and disease, looking at both milk from its evolutionary purpose, how it's evolved to help pattern the immune system and really every organ system in the developing.

baby's body, but also how that donor milk can be used to support a maternal breastfeeding journey. And that's really where I've been incredibly surprised by the results that we've had at heart and what we're hoping to formalize into a full randomized control trial over the next year. 

Lan-Lan: Yeah, I was going to ask are there benefits for the donors as well because there's increasing evidence that it's good for the children in terms of long term obesity because breastfed babies only take as much milk as they need.

Yes, 

Natalie: so that's really fascinating because what we're starting to understand is just how complex human milk is. We've always known it's complex, but it's absolutely tailor made to each individual baby's genetic background, their environmental background, what pathogens they and their mother are exposed to the responsiveness of antibody production of how the breast's very specific immune system works uniquely to make sure that viruses don't pass into breast milk in their entirety in terms of how the microbiome.

is not only supported directly by bacteria from the mother's breast patterning the infant gut, but how certain components of breast milk like the fatty acids and the human milk oligosaccharides, which are very unique as a species. We have over 200. Completely unique described oligosaccharides, so very complex and rich biochemistry of the sugar produced by the lactating mother, and 20 of those oligosaccharides can't be metabolized by the baby, and they're there to feed the gut microbiome.

Specifically the bifidobacteria, the lacto basi, which we know helps pattern a normal, diverse infant microbiome and potentially affect how that baby's brain develops in probably other organ systems too. What we know is that even having a single dose of formula affects the development of that infant microbiome.

It's probably going to be more complex, the use of antibiotics, antenatal care, all sorts of other factors pointing into that. But a critical piece of the jigsaw is how babies are fed. And having a diet of exclusive human milk is becoming seen as more important than it should be. Now the problem is, if a mum is struggling to produce milk and has just been told by a doctor that it's the best way for her baby to have the safer outcomes, the better outcomes, then the most brilliant way to interrupt lactation is to make a mother stressed.

It's completely against how we've evolved to, to lactate. And so by offering donor milk as a bridge, and the communication is really important in this, but if it's set up as a way that we're going to support you, there will be a few days before you get going perhaps, or it might happen very quickly, but your milk will come in.

And in the meantime, we're going to keep baby as safe as possible with access to donor milk. Then it becomes a very different conversation to we're going to need 20 mils in the next two hours. And here's a pump, which we hear over and over again. And then the mother is frantically trying to express and particularly over COVID has often been left alone to do this.

And we've seen breastfeeding rates in neonatal units plummet as a result. 

Lan-Lan: Oh, that is really challenging. We'll get back to some more of the challenges that we've had during the COVID pandemic in particular, but I'm interested in, you were involved in setting up the Hearts Milk Bank. What were the biggest challenges you faced in the process?

Natalie: It's always been money. There has never been a lack of donors. We've always had more milk and more milk donors than we've strictly needed. And that's been fantastic because we've been able to support not only the donors, but more mothers in the community outside of NHS funding than would have received donor milk.

But it was always the logistics and the infrastructure of the milk bank in the middle that's been the issue. And especially the trained staff who have amazing skills, not only in the preparation, the safe preparation of the milk, but in the support of milk donors and in the support of mothers who receive it.

It's a very specialized service. And one of the really exciting opportunities that we're creating through the charity is a training program, which will effectively serve to professionalize the service and mean that these very unique skills can be put to better effect by more people. 

Lan-Lan: That's really interesting.

It's interesting that you said that you've got more people interested in donating than you have the capacity to handle. If someone did want to become a donor, how would they go about doing so? 

Natalie: In the UK, the milk banks are listed on a website by the UK Association for Milk Banking, ucam. org, and you can find all the milk bank contact details there.

And then we've got our websites as well. We have been quite unique as a milk bank because we didn't have a cutoff of the baby's age depending on how long the mom could donate for or so on. And that's really evidence based from limited amounts of evidence that we're looking to add to that shows that human milk actually changes only very slightly over the first 24 months of lactation, certainly from both a microbiota point of view, but also a fatty acid and metabolomics.

point of view. And that's actually milk seems to become more concentrated as the infant goes over their first year. And that's probably because they're feeding less often. So it becomes a more concentrated fluid, but also the concentrations of antimicrobial components like lactoferrin and lysozyme, they go up.

And that could be really important for preterm babies as well as having more calories from from the more concentrated milk donations. 

Lan-Lan: That's really interesting. And you did. touch on some of the logistical issues. Now, one thing that I've been curious, how do you go about distributing the milk?

Natalie: So we work with an amazing charity called Serve, who work in regional county groups, and they are a group of volunteer bikers. They also drive cars as well. And they work for free for the NHS and for organizations like ourselves to distribute blood products, medical records, pharmacy products, and critically donor milk.

So that enables us to have basically a national logistics capability. We've sent milk overseas to Ireland when the milk bank in Northern Ireland had some problems. That was by plane with dry ice and it was a lot more difficult than working with the volunteer groups. But we get milk out at the moment to over 30 hospitals and over 20 different families every month.

So it's become a huge logistical challenge, which we're rising to. 

Lan-Lan: Yeah, that's fantastic. I actually do have a friend who was involved in one of these milk runs where she got on her motorbike in the dead of night and ferried some of it from one place to another. So it's it 

Natalie: can be quite dramatic.

The charity has also been gifted a milk mobile by our charity partner at some UK, the printer company. And so I'm looking at it in the car park at the moment, it's a little smart car and that whizzes around and picks up all the milk from local donors. So that takes some of the pressure off them. the volunteers.

And it's also really fun to drive.

Lan-Lan: Definitely. So there's so many, we touched on this a little bit earlier, but there are so many myths that surround breastfeeding and milk banks. What's the one that you would like to bust the most? 

Natalie: Oh, do I have to pick one?

So from a neonatal unit perspective, it's the. twin myth of cost and availability, and we hear this over and over again. There need not be a lack of availability of donor milk into hospitals, and we've modelled this with a great team from Exeter University. We've got a PhD student who's going to be looking at this over the next few years, but we've got plans based on that early modelling work.

to be able to supply effectively every baby born under 34 weeks, plus those with cardiac anomalies and other situations, we can ramp up over the next three years to meet that demand nationally. So there really is no problem with availability. In terms of cost, we know that very low birth weights fed. Babies fed with donor milk on average go home a day early.

That saves a cost to the NHS of between a thousand and two thousand pounds in intensive care costs. They tolerate feeds better, they go up to full feeds more quickly. They come off TPN, which is an expensive form of nutrition, earlier. And every day of doing donor milk effectively costs around 7. 50 to 20.

So the cost savings are huge. And the real money shot, if you can call it that, of having access to donor milk is that it can improve breastfeeding rates where it's used in the context of optimal lactation support. And that's for the reasons I explained earlier, it takes. the pressure off of mums who are desperately trying to establish a supply.

So cost availability, the fact that it's not only useful for preterm babies and by having artificial cutoffs, that's another great way. It's not great at all. Forgive my sarcasm, but it's another way that it. puts pressure on mothers and increasingly we've had phone calls often from the fathers who are trying to advocate for their partners where the cutoff on the unit is a strict 30 weeks and their babies have been born at 30 plus three and it's completely arbitrary and so if we can crack the issue of availability by creating a big enough milk bank, then not only do we relieve this false rationing, but we also make it a cheaper service as well by the economies of scale that are built in.

And the third one I would go for is the medical principle that giving formula does no harm. And I think there's an increasing body of evidence that shows that's not the case. And I think parents starting to understand that increasingly and. Ask for access to donor milk. And it's interesting that in 2016, the UN declared breastfeeding a human right, a basic child right.

What happens when breastfeeding isn't possible? And it's going to be interesting to explore the legalities of whether there should be access to donor milk, if that's what the parents are wishing. 

Lan-Lan: Leading on from those three topics. What's your biggest concern for milk banks and breastfeeding right now?

Natalie: I, there are so many challenges. I polled my medical friends of colleagues of what they felt this morning, and there are so many. So largely it comes down to demoralization and an underfunding of breastfeeding support services. We know that services have gone down by nearly 50 percent over the last 10 years for that women can access in their communities.

that infant feeding teams are often stretched and being asked to cover increasingly not only the NICU but the postnatal ward and now the community services as well as health visitors are redeployed during COVID. We've just had a paper accepted where we polled 1, 200 women and found that a significant proportion of those had fairly disastrous breastfeeding experiences, 80 percent introducing formula when they had never wanted to or wished to, but simply because they're not able to access support.

And it's hugely demoralizing for the people working in that, primarily women who are trying to do their best, but don't have the funds or the support or the team to be able to offer the service that they know is needed. And, COVID amongst everything has been very challenging for milk bank services globally.

Lan-Lan: I was just going to ask you, how have things been for your milk bank and the charity during this pandemic? 

Natalie: Sure. Things have been hectic because we always. work towards mitigating any challenges to safety because obviously the bulk of the donor milk is going to the most exceptionally vulnerable preterm babies.

And we know from our history that HIV was what pretty much put the death knell into any sort of national service 40 years ago. So the imperative was really to understand how coronaviruses worked in breast milk, whether antibodies were produced, whether we could use that at the same a potential therapeutic, but critically what steps the breast, the milk banks needed to put in place to make sure that their services, our services remained safe and that our team, donors, volunteers were all kept safe during the pandemic.

To do that, something quite remarkable happened in that we set up a virtual communication group and asked with my colleague, Gillian Weaver, who is an international milk bank consultant, we asked people from different countries to come on board. And within two weeks we had over 35 countries represented.

Wow. That's fantastic. 40. And that's currently formalizing into a global alliance of milk banks and milk bank associations. And every populated continent is represented. We've published a call to action in the Lancet child and adolescent health. We've been able to respond very quickly to.

Papers that have come out that have perhaps misrepresented how breastfeeding immunology works and the collaborative and basically support network that's created has really surpassed anything that I thought would be possible. And has been. If there can be a positive to come out of the pandemic, then it's been a true positive that I hope will serve us well in the future.

Lan-Lan: Fantastic. That is good to hear that it's kicked off some good things in the world. And so just continuing on that good note. Where do you see milk banking going in the future? 

Natalie: I think it's a fantastically exciting time as a medic, as somebody who is witnessing the impacts on preventative medicine.

For anybody interested in setting up an entire new field of medicine, then this is it. But it can't work alone. Donor milk used in isolation without lactation supporters is potentially just as bad in many ways as a breast milk substitute. And I was saying last week that if we managed to establish an absolutely fantastic technologically advanced service over the next five years, but see no change in breastfeeding rates in the UK, then we will have utterly failed.

And what we're doing now is laying the foundations of research trials that are looking at embedding lactation support with access to donor milk as a supplement if needed. into postnatal midwifery services health visitor services, and potentially even A& E and postnatal ward services in our local communities.

It's a fantastically exciting time. We're really trailblazing at the moment without overusing that word, but there isn't a Google for this. It's a, it's an interesting time. 

Lan-Lan: Yeah. That's wonderful. I feel like I've learned so much just from this quick chat that we've had, and I hope that our listeners have found it informative as well.

So I am personally, I'm definitely looking forward to reading the results of your clinical trials and research that you're doing. And I thank you. Thank you so much for talking to us today about the really important work that you're doing. I just want 

Natalie: to thank everybody who supported the charity. It's been quite a journey over the last four years, but especially UKRI and Imperial College, who are supporting me to do the really needed research in this sector.

Nothing would happen without all the milk donors and the volunteers in the charity. 

Lan-Lan: Thank 

Natalie: you. Wonderful. 

Lan-Lan: Thank you, Natalie. It's been a pleasure and I'll sign off now. Goodbye. Thanks. 

Gavin: Thank you so much to Lanlan and Natalie for talking about Hearts Milk Bank. You can find out more at heartsmilkbank.

org, including their current fundraising campaign. 

Jessamy: Thank you for listening to this episode of The Lancet Boys. You can subscribe to us wherever you normally get your podcasts, and we hope to see you next time.